The contract will continue a natural history study of human papillomavirus (HPV) infection and cervical neoplasia. The study has been underway since the early 1990s. The original enrollment was approximately 10,000. We are following selected subcohorts totalling about 6,000 women for specific objectives. Most importantly, we aim to understand better the origins of high-grade squamous intraepithelial lesions (HSIL), the direct precursors to invasive cervical cancer. Cases of HSIL occurring in the cohort will be studied extensively, to understand their origins related to HPV infection. Also, by continuing to study HPV infection on a visual, microscopic, molecular, and serologic level for each woman multiple times, we hope to characterize the natural history of HPV infection in a population. This natural history work is leading to the Phase 3 trial of the NCI HPV vaccine study, scheduled to begin in about 2-3 years. Therefore, we are performing a great deal of methodologic work on the host response to HPV as well.